Inhibitors of sterol synthesis. Synthesis and spectral properties of 3 β -hydroxy-25,26,26,26,27,27,27-heptafluoro-5 α -cholestan-15-one

3 β -Hydroxy-25,26,26,26,27,27,27-heptafluoro-5 α -cholestan-15-one ( 4 ) has been prepared as part of a program to synthesize 15-ketosterols that are not readily metabolized to cholesterol or side-chain oxygenated species. Saponification of 3 β -acetoxy-5 α -chola-8(14),23-dien-15-one ( 5 ) followed by lithium-ammonia reduction with a bromobenzene quench gave 3 β -hydroxy-5 α -chol-23-en-15-one ( 6 ). Addition of (CF 3 ) 2 CFI to 6 in the presence of triethylborane gave an iodide preparation, which was reduced to 4 with tributyltin hydride (71% overall yield of 4 from 5 ). The 23-iodide preparations consisted of 6:1 mixtures of (23 R )-3 β -hydroxy-23-iodo-25,26,26,26,27,27,27-heptafluoro-5 α -cholestan-15-one ( 9a ) and its C-23 epimer 9b with variable amounts of 4. Compound 4 was also prepared by lithium-ammonia reduction of the Δ 8(14) analogs of 4 and iodides 9a and 9b. The presence of small amounts of 6 in the latter product suggested a side reaction involving cleavage of the C24–C25 bond with loss of a (CF 3 ) 2 CF· radical. Also prepared were 25,26,26,26,27,27,27-heptafluoro-5 α -cholestane-3 β,15 α -diol, its 15 β epimer, the 7 α -methyl analog of 4, 3 β -hydroxy-7 α -methyl-5 α -cholestan-15-one ( 16 ), and (25 R )-3 β,26-dihydroxy-5 α -cholestan-15-one. Full 1 H and 13 C-NMR data of high precision with complete signal assignments are given for all new compounds. Definitive 1 H-NMR stereochemical assignments of the C-24 protons were established for most sterols with a C 8 H 17 side chain based on analysis of the downfield H-24 resonance in a 750-MHz spectrum of 16. Detailed electron-impact mass spectral data are presented together with a summary of major fragmentation patterns for 15-hydroxy- and 15-ketosteroids with and without a Δ 8(14) bond.